Protective effect of trans-nerolidol on vascular endothelial cell injury induced by lipopolysaccharides / Efectos protectores del trans-nerolidol en lesiones inducidas por lipopolisacáridos en células endoteliales vasculares

This article aimed to discuss the protection of trans - nerolidol on vascular endothelial cells (ECs) injured by lipopolysac charides. ECs were divided into four groups: normal, model, low and high dose trans - nerolidol treatment groups. The cell survival rate and the contents of NO in the cell culture supernatant were determined. The protein expression and transcript level of pe roxisome proliferator - activated receptor - γ (PPARγ), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) were determined by western blotting and RT - PCR respectively. Compared with the normal group, cell livability, protein e xpression and mRNA transcript level of PPARγ and eNOS decreased, NO contents, protein expression and mRNA transcript tlevel of iNOS increased in model group significantly. Compared with model group, all the changes recovered in different degree in treatmen t groups. Hence, it was concluded that trans - nerolidol can alleviate the ECs injuryby the regulation of iNOS/eNOS through activating PPARγ in a dose - dependent manner

Este artículo tiene como objetivo discutir la protección del trans - nerolidol en las células endoteliales vasculares (CE) dañadas por lipopolisacáridos. Las CE se di vidieron en cuatro grupos: normal, modelo, grupos de tratamiento con trans - nerolidol de baja y alta dosis. Se determinó la tasa de supervivencia de las células y los contenidos de óxido nítrico (NO) en el sobrenadante del cultivo celular. La expresión de p roteínas y el nivel de transcripción del receptor activado por proliferadores de peroxisomas - γ (PPARγ), el óxido nítrico sint et asa endotelial (eNOS) y el óxido nítrico sint et asa inducible (iNOS) se determinaron mediante western blot y RT - PCR, respectivamen te. En comparación con el grupo normal, la viabilidad celular, la expresión de proteínas y el nivel de transcripción de PPARγ y eNOS disminuyeron, los contenidos de NO, la expresión de proteínas y el nivel de transcripción de iNOS aumentaron significativam ente en el grupo modelo. En comparación con el grupo modelo, todos los cambios se recuperaron en diferentes grados en los grupos de tratamiento. Por lo tanto, se concluyó que el trans - nerolidol puede aliviar el daño en las CE regulando iNOS/eNOS a través d e la activación de PPARγ de manera dependiente de la dosis.

A prediction model for coronary artery abnormalities in children with Kawasaki disease older than 5 years

Abstract Objective: Reliably prediction models for coronary artery abnormalities (CAA) in children aged > 5 years with Kawasaki disease (KD) are still lacking. This study aimed to develop a nomogram model for predicting CAA at 4 to 8 weeks of illness in children with KD older than 5 years. Methods: A total of 644 eligible children were randomly assigned to a training cohort (n = 450) and a validation cohort (n = 194). The least absolute shrinkage and selection operator (LASSO) analysis was used for optimal predictors selection, and multivariate logistic regression was used to develop a nomogram model based on the selected predictors. Area under the receiver operating characteristic curve (AUC), calibration curves, Hosmer-Lemeshow test, Brier score, and decision curve analysis (DCA) were used to assess model performance. Results: Neutrophil to lymphocyte ratio, intravenous immunoglobulin resistance, and maximum baseline z-score ≥ 2.5 were identified by LASSO as significant predictors. The model incorporating these variables showed good discrimination and calibration capacities in both training and validation cohorts. The AUC of the training cohort and validation cohort were 0.854 and 0.850, respectively. The DCA confirmed the clinical usefulness of the nomogram model. Conclusions: A novel nomogram model was established to accurately assess the risk of CAA at 4-8 weeks of onset among KD children older than 5 years, which may aid clinical decisionmaking.

The lncRNA-MALAT1/miR-330-3p Axis Promotes Growth and Metastasis of Gastric Cancer Through Regulation of Vascular Endothelial Growth Factor A: A Genetic and Cell Evaluation Study

SUMMARY: Overexpression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in various tumor tissues and cell lines was found to promote tumor cell proliferation, migration, and invasion. However, the role of MALAT1 in gastric cancer (GC) is still unclear. We aimed to investigate the correlation between long-chain non-coding RNAs (lncRNAs), MALAT1, MicroRNAs (miRNA) and vascular endothelial growth factor A (VEGFA) in gastric cancer and to disclose underlying mechanism. The correlation between MALAT1 levels and clinical features was analyzed by bioinformatics data and human samples. The expression of MALAT1 was down regulated in AGS cells to detect the cell proliferation, migration, and invasion characteristics, as well as the effects on signal pathways. Furthermore, we validated the role of MALAT1/miR-330-3p axis in GC by dual luciferase reporter gene assays. Expression of MALAT1 was higher in cancer tissues than in para-cancerous tissues. The high MALAT1 level predicted malignancy and worse prognosis. Down-regulation of MALAT1 expression in AGS cells inhibited cell proliferation, migration, and invasion by targeting VEGFA. By dual luciferase reporter gene assay and miR-330-3p inhibitor treatment, we demonstrate that MALAT1 sponged miR-330-3p in GC, leading to VEGFA upregulation and activation of the mTOR signaling pathway. The MALAT1/miR-330-3p axis regulates VEGFA through the mTOR signaling pathway and promotes the growth and metastasis of gastric cancer.

Se descubrió que la sobreexpresión del transcrito 1 de adenocarcinoma de pulmón asociado a metástasis (MALAT1) en varios tejidos tumorales y líneas celulares promueve la proliferación, migración e invasión de células tumorales. Sin embargo, el papel de MALAT1 en el cáncer gástrico (CG) aún no está claro. Nuestro objetivo fue investigar la correlación entre los ARN no codificantes de cadena larga (lncRNA), MALAT1, los microARN (miARN) y el factor de crecimiento endotelial vascular A (VEGFA) en el cáncer gástrico y revelar el mecanismo subyacente. La correlación entre los niveles de MALAT1 y las características clínicas se analizó mediante datos bioinformáticos y muestras humanas. La expresión de MALAT1 se reguló negativamente en las células AGS para detectar las características de proliferación, migración e invasión celular, así como los efectos sobre las vías de señales. Además, validamos el papel del eje MALAT1/miR- 330-3p en GC mediante ensayos de genes indicadores de luciferasa dual. La expresión de MALAT1 fue mayor en tejidos cancerosos que en tejidos paracancerosos. El alto nivel de MALAT1 predijo malignidad y peor pronóstico. La regulación negativa de la expresión de MALAT1 en células AGS inhibió la proliferación, migración e invasión celular al apuntar a VEGFA. Mediante un ensayo de gen indicador de luciferasa dual y un tratamiento con inhibidor de miR-330-3p, demostramos que MALAT1 esponjaba miR-330-3p en GC, lo que lleva a la regulación positiva de VEGFA y la activación de la vía de señalización mTOR. El eje MALAT1/miR-330-3p regula VEGFA a través de la vía de señalización mTOR y promueve el crecimiento y la metástasis del cáncer gástrico.

Diagnostic utility, disease activity, and disease phenotype correlation of serum ASCA, pANCA, and PR3-ANCA in pediatric inflammatory bowel disease

Abstract Objective: This study aimed to evaluate the diagnostic utility, disease activity, and phenotypic association of serum anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), PR3-ANCA, and MPO-ANCA in pediatric patients with inflammatory bowel disease (IBD). Methods: Pediatric patients diagnosed with IBD were recruited and classified as Crohn's disease (CD), ulcerative colitis (UC), and IBD-unclassified (IBD-U) through full investigation. The Paris classification was used to evaluate disease phenotypes of pediatric CD and UC. Results: In all, 229 pediatric patients with IBD (CD 147, UC 53, IBD-U 29) were included. The ASCA IgG seropositivity significantly differed among the three groups (CD 75.4%, UC 17.5%, and IBD-U 60.0%; p < 0.001). PR3-ANCA positive rates were the highest in UC (24.0%), followed by IBD-U (17.6%), and none in CD (p = 0.002); pANCA-positive rates were higher in IBD-U (33.6%), followed by UC (28.0%) than in CD (1.4%) (p < 0.001). Regarding disease phenotype, perianal disease revealed higher serum ASCA IgG titers (median 36.7 U/mL in P1 vs. 25.2 U/mL in P0, p = 0.019). Serum ASCA IgG and IgA cutoff values to distinguish CD were 32.7 (U/mL) and 11.9 (U/mL), respectively, with a specificity of 80.0%. Conclusion: Serological biomarkers of ASCA IgG and IgA were effective for differentiating CD in pediatric IBD patients, and serum pANCA and PR3-ANCA, but not MPO-ANCA, were effective in distinguishing UC and IBD-U. Furthermore, measuring serological titers of ASCA IgG and IgA may help differentiate CD and evaluate the disease activity and phenotype of pediatric IBD in practice.

The essential role of adenine nucleotide translocase 4 on male reproductive function in mice

Adenine nucleotide translocator 4 (Ant4), an ATP/ADP transporter expressed in the early phases of spermatogenesis, plays a crucial role in male fertility. While Ant4 loss causes early arrest of meiosis and increased apoptosis of spermatogenic cells in male mice, its other potential functions in male fertility remain unexplored. Here, we utilized Ant4 knockout mice to delineate the effects of Ant4-deficiency on male reproduction. Our observations demonstrated that Ant4-deficiency led to infertility and impaired testicular development, which was further investigated by evaluating testicular oxidative stress, autophagy, and inflammation. Specifically, the loss of Ant4 led to an imbalance of oxidation and antioxidants. Significant ultrastructural alterations were identified in the testicular tissues of Ant4-deficient mice, including swelling of mitochondria, loss of cristae, and accumulation of autophagosomes. Our results also showed that autophagic flux and AKT-AMPK-mTOR signaling pathway were affected in Ant4-deficient mice. Moreover, Ant4 loss increased the expression of pro-inflammatory factors. Overall, our findings underscored the importance of Ant4 in regulating oxidative stress, autophagy, and inflammation in testicular tissues. Taken together, these insights provided a nuanced understanding of the significance of Ant4 in testicular development.

Transcription Factor E2F7 Activates PKMYT1 to Partially Suppress Adriamycin Sensitivity in Gastric Cancer Through the MAPK Signaling Pathway

ABSTRACT Background: Adriamycin (ADM) resistance remains an obstacle to gastric cancer chemotherapy treatment. Objective: The objective of this study was to study the role and mechanism of transcription factor E2F7 in sensitivity to ADM chemotherapeutic agents in gastric cancer. Methods: Cell viability and cell sensitivity were assessed by CCK-8 and IC50 values of ADM were calculated. The impact of ADM on cellular proliferative capacity was assessed through colony formation assay. The binding relationship between E2F7 and PKMYT1 was then verified by dual luciferase assay and chromatin immunoprecipitation assay. ERK1/ERK2 and p-ERK1/p-ERK2 protein expression levels were detected by western blot. Results: In both gastric cancer tissue and ADM-resistant cells, a conspicuous upregulation of E2F7 and PKMYT1 was observed. Upregulated PKMYT1 was notably enriched in the MAPK signaling pathway. Enhanced levels of E2F7 were shown to not only drive gastric cancer cell proliferation but also engender a reduction in the sensitivity of these cells to ADM. Furthermore, PKMYT1 emerged as a downstream target of E2F7. Activation of E2F7 culminated in the transcriptional upregulation of PKMYT1, and silencing E2F7 reversed the inhibitory impact of PKMYT1 overexpression on ADM sensitivity in gastric cancer cells. Conclusion: E2F7/PKMYT1 axis might promote the proliferation and partially inhibit ADM sensitivity of gastric cancer cells by activating the MAPK pathway.

Puerarin protects the fatty liver from ischemia-reperfusion injury by regulating the PI3K/AKT signaling pathway

Abstract The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway.

Small Molecules Accelerate Skin Wound Healing: Shikonin Efficacy and Mechanism of Action in Mice / Las Moléculas Pequeñas Aceleran la Curación de Heridas en la Piel: Eficacia de Shikonin y Mecanismo de Acción en Ratones

SUMMARY: The objective of this study was to investigate the therapeutic wound healing potential and molecular mechanisms of shikonin as small molecules in vitro. A mouse burn model was used to explore the potential therapeutic effect of shikonin; we traced proliferating cells in vivo to locate the active area of skin cell proliferation. Through the results of conventional pathological staining, we found that shikonin has a good effect on the treatment of burned skin and promoted the normal distribution of skin keratin at the damaged site. At the same time, shikonin also promoted the proliferation of skin cells at the damaged site; importantly, we found a significant increase in the number of fibroblasts at the damaged site treated with shikonin. Most importantly, shikonin promotes fibroblasts to repair skin wounds by regulating the PI3K/AKT signaling pathway. This study shows that shikonin can effectively promote the proliferation of skin cell, and local injection of fibroblasts in burned skin can play a certain therapeutic role.

El objetivo de este trabajo fue investigar el potencial terapéutico de cicatrización de heridas y los mecanismos moleculares de la shikonina como moléculas pequeñas in vitro. Se utilizó un modelo de quemaduras en ratones para explorar el posible efecto terapéutico de la shikonina; Rastreamos las células en proliferación in vivo para localizar el área activa de proliferación de células de la piel. A través de los resultados de la tinción para patología convencional, encontramos que la shikonina tiene un buen efecto en el tratamiento de la piel quemada y promueve la distribución normal de la queratina de la piel en el sitio dañado. Al mismo tiempo, la shikonina también promovió la proliferación de células de la piel en el sitio dañado. Es importante destacar que encontramos un aumento significativo en la cantidad de fibroblastos en el sitio dañado tratado con shikonina. Lo más importante es que la shikonina promueve la función reparadora de fibroblastos en las heridas de la piel regulando la vía de señalización PI3K/ AKT. Este estudio muestra que la shikonina puede promover eficazmente la proliferación de células de la piel y que la inyección local de fibroblastos en la piel quemada puede desempeñar un cierto papel terapéutico.

Minimally invasive ureteroplasty with lingual mucosal graft for complex ureteral stricture: analysis of surgical and patient-reported outcomes

ABSTRACT Objective: To evaluate objective treatment efficacy and safety, and subjective patient-reported outcomes in patients with complex ureteral strictures (US) undergoing minimally invasive lingual mucosal graft ureteroplasty (LMGU). Materials and Methods: We prospectively enrolled patients underwent robotic or laparoscopic LMGU between May 2020 and July 2022. Clinical success was defined as symptom-free and no radiographic evidence of re-obstruction. Patient-reported outcomes, including health-related quality of life (HRQoL), mental health status and oral health-related quality of life (OHRQoL), were longitudinally evaluated before surgery, 6 and 12 months postoperatively. Results: Overall, 41 consecutive patients were included. All procedures were performed successfully with 32 patients in robotic approach and 9 in laparoscopic. Forty (97.56%) patients achieved clinical success during the median follow-up of 29 (range 15-41) months. Although patients with complex US experienced poor baseline HRQoL, there was a remarkable improvement following LMGU. Specifically, the 6-month and 12-month postoperative scores were significantly improved compared to the baseline (p < 0.05) in most domains. Twenty-eight (68.3%) and 31 (75.6%) patients had anxiety and depression symptoms before surgery, respectively. However, no significant decrease in the incidence of these symptoms was observed postoperatively. Moreover, there was no significant deterioration of OHRQoL at 6 months and 12 months postoperatively when compared to the baseline. Conclusions: LMGU is a safe and efficient procedure for complex ureteral reconstruction that significantly improves patient-reported HRQoL without compromising OHRQoL. Assessing patients' quality of life enables us to monitor postoperative recovery and progress, which should be considered as one of the criteria for surgical success.

5HT2A modulation attenuates pancreatic cancer induced pain mouse model by inhibiting HDAC

ABSTRACT Purpose: Patients have been severely suffered from cancer associated pain, and pancreatic cancer is the most severe form of cancer associated with pain. There are very few options available to manage it. The present report evaluated the effect of 5HT2A on pancreatic cancer associated pain. Methods: Pancreatic cancer was induced by injecting SW 1,990 cells (~3×106in a 20 μL suspension) into the pancreas and formed a 2-3-mm vesicle using an inoculator fitted with a 26-gauge needle in BALB/c-nu mice. Survival rate and body weight of the mice were observed. Pain behaviour testing was performed at the end of each week (third and fourth week) after surgery. Inflammatory mediators and HDAC 2 proteins were determined in the spinal tissue using quantitative real-time polymerase chain reaction. Results: There was improvement in the survival rate and body weight in 5HT2A antagonist treated group than pancreatic cancer group of mice. Moreover, 5HT2A antagonist ameliorated the alteration in pain behaviour of pancreatic cancer mice. mRNA expression of HDAC2 and level of inflammatory cytokines were reduced in the spinal tissue of 5HT 2A antagonist treated group than pancreatic cancer group of mice. Conclusions: Data revealed that 5HT2A antagonist ameliorates pain associated with pancreatic cancer mice by HDAC inhibition and inflammatory cytokines. The result of investigation supports that modulation of 5HT2A receptor could be used clinically to protects neuropathic pain in pancreatic cancer.

Effect size varies based on calculation method and may affect interpretation of treatment effect: an illustration using randomised clinical trials in osteoarthritis

Abstract Background To illustrate how (standardised) effect sizes (ES) vary based on calculation method and to provide considerations for improved reporting. Methods Data from three trials of tanezumab in subjects with osteoarthritis were analyzed. ES of tanezumab versus comparator for WOMAC Pain (outcome) was defined as least squares difference between means (mixed model for repeated measures analysis) divided by a pooled standard deviation (SD) of outcome scores. Three approaches to computing the SD were evaluated: Baseline (the pooled SD of WOMAC Pain values at baseline [pooled across treatments]); Endpoint (the pooled SD of these values at the time primary endpoints were assessed); and Median (the median pooled SD of these values based on the pooled SDs across available timepoints). Bootstrap analyses were used to compute 95% confidence intervals (CI). Results ES (95% CI) of tanezumab 2.5 mg based on Baseline, Endpoint, and Median SDs in one study were - 0.416 (- 0.796, - 0.060), - 0.195 (- 0.371, - 0.028), and - 0.196 (- 0.373, - 0.028), respectively; negative values indicate pain improvement. This pattern of ES differences (largest with Baseline SD, smallest with Endpoint SD, Median SD similar to Endpoint SD) was consistent across all studies and doses of tanezumab. Conclusion Differences in ES affect interpretation of treatment effect. Therefore, we advocate clearly reporting individual elements of ES in addition to its overall calculation. This is particularly important when ES estimates are used to determine sample sizes for clinical trials, as larger ES will lead to smaller sample sizes and potentially underpowered studies. Trial Registration Clinicaltrials.gov NCT02697773, NCT02709486, and NCT02528188.

Associations of serum gamma-linolenic acid levels with erythema severity and anxiety/depression status in patients with rosacea

Abstract Background The development of rosacea is suggested to be closely associated with lipid metabolism, inflammation, and anxiety/depression. Gamma linolenic acid (GLA) is a key factor participating in lipid metabolism, which is also confirmed to regulate the inflammatory response. However, the associations of serum GLA levels with rosacea severity and psychological status still remain unclear. Objective and limitations of the study The present study aimed to investigate the associations of gamma linolenic acid (GLA), a key factor participating in lipid metabolism and the inflammatory response, with rosacea severity and psychological status. The present study still had some limitations. First, this study is a cross-sectional study and does not provide longitudinal evidence about the relationship between GLA and rosacea; Second, the cohort in this study is also relatively small, and a larger cohort is needed in further investigation to reveal the potential role of lipid metabolism in the pathogenesis of rosacea. Methods A total of 62 rosacea patients were consecutively recruited. Patient's Self-Assessment (PSA) scale and Clinician Erythema Assessment (CEA) as well as 7-item Generalized Anxiety Disorder (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9) were conducted to evaluate the degree of erythema severity and anxiety/depression, respectively. Serum GLA levels were determined by gas chromatography mass. Results Lower levels of serum GLA in rosacea patients were observed (p < 0.001), and subgroup analysis revealed that patients with higher-level GLA had lower scores of PSA, CEA, GAD-7 and PHQ-9. Moreover, Spearman correlation analysis uncovered that serum GLA levels were negatively associated with PSA, CEA, GAD-7 as well and PHQ-9 scores, respectively. Linear regression model found that serum GLA levels at baseline were a predictive factor for prognosis of clinical outcomes after 1-month conventional treatment. Conclusion The present study indicates that lower levels of serum GLA in rosacea patients are negatively associated with the degree of erythema and anxiety/depression status.

Minimum effective concentration of ropivacaine for ultrasound-guided transmuscular quadratus lumborum block in total hip arthroplasty: a randomized clinical trial

Abstract Objective: This trial aimed to identify the Minimum Effective Concentration (MEC90, defined as the concentration which can provide successful block in 90% of patients) of 30 mL ropivacaine for single-shot ultrasound-guided transmuscular Quadratus Lumborum Block (QLB) in patients undergoing Total Hip Arthroplasty (THA). Methods: A double-blind, randomized dose-finding study using the biased coin design up-and-down sequential method, where the concentration of local anesthetic administered to each patient depended on the response from the previous one. Block success was defined as a Numeric Rating Scale (NRS) score during motion ≤ 3 at 6 hours after arrival in the ward. If the block was successful, the next subject received either a 0.025% smaller dose (probability of 0.11) or the same dose (probability of 0.89); otherwise, the next subject received a 0.025% higher ropivacaine concentration. MEC90, MEC95 and MEC99 were estimated by isotonic regression, and the corresponding 95% Confidence Intervals (95% CIs) were calculated by the bootstrapping method. Results: Based on the analysis of 52 patients, MEC90, MEC95, and MEC99 of ropivacaine for QLB were estimated to be 0.352% (95% CI 0.334-0.372%), 0.363% (95% CI 0.351-0.383%), and 0.373% (95% CI 0.363-0.386%). The concentration of ropivacaine at 0.352% in a volume of 30 ml can provide a successful block in 90% of patients. Conclusions: For ultrasound-guided transmuscular QLB in patients undergoing THA, 0.352% ropivacaine in a volume of 30 ml can provide a successful block in 90% of patients. Further dose-finding studies and large sample size are required to verify the concentration.

Serotype distribution and antimicrobial resistance of pediatric Streptococcus pneumoniae isolated from inpatients and outpatients at Beijing Children's Hospital

Abstract Background Understanding the epidemiology of Streptococcus pneumoniae (S. pneumoniae) isolates is important for pneumonia treatment and prevention. This research aimed to explore the epidemiological characteristics of S. pneumoniae isolated from pediatric inpatients and outpatients during the same period. Methods S. pneumoniae were isolated from unsterile samples of inpatients and outpatients younger than five years old between March 2013 and February 2014. The serotypes were determined using diagnostic pneumococcal antisera. The resistance of each strain to 13 antibiotics was tested using either the E-test or the disc diffusion method. The Sequence Types (STs) were analyzed via Multilocus Sequence Typing (MLST). Results The dominant serotypes obtained from inpatients were 19F (32.9 %), 19A (20.7 %), 23F (10.7 %), 6A (10.0 %), and 14 (8.6 %), while those from outpatients were 19F (13.6 %), 23F (12.9 %), 6A (10.0 %), 6B (10.0 %), and 19A (7.9 %). The coverage rates of 13-valent Pneumococcal Conjugate Vaccine (PCV) formulations were high in both groups. The nonsusceptibility to penicillin, cefuroxime, imipenem, erythromycin, and trimethoprim-sulfamethoxazole among the inpatient isolates was 7.1 %, 92.8 %, 65.7 %, 100 %, and 85.0 %, respectively, while that among the outpatient isolates was 0.7 %, 50.0 %, 38.6 %, 96.4 %, and 65.7 %, respectively. There were 45 and 81 STs detected from the pneumococci isolated from inpatients and outpatients, respectively. CC271 was common among both inpatients and outpatients (43.6 % and 14.3 %). Conclusions Pneumococcal vaccine-related serotypes are prevalent among both inpatients and outpatients, especially among inpatients, who exhibit more severe antibiotic resistance. Therefore, universal immunization with PCV13 would decrease the hospitalization rate due to S. pneumoniae and the antibiotic resistance rate of S. pneumoniae.

Anlotinib suppressed tumor cell proliferation and migration in hypopharyngeal carcinoma

Abstract Objective The purpose of this study is to study the in-vitro effects of multitarget inhibitor anlotinib on hypopharyngeal cancer cell proliferation and cell migration, and the underlying mechanism, which will provide new drug choices for hypopharyngeal cancer treatment. Methods The Hypopharyngeal cancer Fadu cells were treated with anlotinib at a concentration of 0, 5, and 10 μmoL/L, respectively. Cell counting kit-8 and the colony-forming assay were used to detect the inhibition of cell proliferation. Wound-healing assay and transwell assay were used to detect the migration and invasion ability of cells. Flow cytometry was used to detect the effects of anlotinib on cell cycle and apoptosis. RT-qPCR and Western blot were used to measure gene expression levels. Results CCK-8 and colony-forming assay showed that anlotinib could significantly inhibit cell proliferative activity. Wound-healing assay and transwell assay showed that anlotinib could inhibit cell migration and scratch. These results showed that anlotinib has obvious antitumor activity. Flow cell cycle experiment showed that anlotinib could promote Fadu cell apoptosis and block the G2/M phase for inhibiting cell proliferation. In addition, anlotinib decreased the expression of HIF-1α. Conclusions Anlotinib has an excellent suppressing effect on the proliferation, migration, and invasion of hypopharyngeal cancer Fadu cells in-vitro. Moreover, it can play an anti-tumor role through blocking cell cycle G2/M and promoting apoptosis, which may be related to the decrease of HIF-1a expression. Our study would provide a potential treatment method for patients with hypopharyngeal cancer. Level of evidence: Level 3.

Physical activity, anxiety, depression, and coping in Turkish men and women during the first wave of COVID-19 / Atividade física, ansiedade, depressão e enfrentamento em homens e mulheres turcos durante a primeira onda de COVID-19 / Actividad física, ansiedad, depresión y afrontamiento en hombres y mujeres turcos durante la primera ola de COVID-19

Abstract: A need exists to better understand the relationships between COVID-19, coping behaviors, physical activity and stress, and COVID-19's impact on way of life. A cross-sectional study design was used to examine adult physical activity, hope, depression, anxiety, and coping status by gender during the COVID-19 pandemic, and to determine the impact of these variables on the coping process. The study also examined the effect of gender on the relation between physical activity and dependent variables. A global survey instrument was used in this study, including 1,400 Turkish adults. This study identified significant gender-based differences regarding physical activity, hope, depression, anxiety, and coping status of adults, although no significant gender-based difference was found regarding hope scores. Furthermore, physical activity directly influenced coping (β = 0.10), hope (β = 0.12), and anxiety (β = -0.08). Hope directly and positively influenced coping (β = 0.45) and directly and negatively influenced anxiety (β = -0.25) and depression (β = -0.28). Moreover, gender did not directly affect physical activity, but it was associated with decreased coping and increased depression and anxiety. Finally, gender had no effect on the relation between physical activity and hope, coping, depression, and anxiety (p > 0.01). These outcomes support the critical importance of physical activity and hope when coping with COVID-19 regardless of gender.

Resumo: Existe uma necessidade de entender melhor as relações entre a COVID-19, comportamentos de enfrentamento, atividade física e estresse e o impacto da COVID-19 no modo de vida. Um desenho de estudo transversal foi usado para examinar a atividade física adulta, esperança, depressão, ansiedade e estado de enfrentamento por gênero durante a COVID-19 e para determinar os efeitos de atividade física, esperança, depressão, e ansiedade no enfrentamento da COVID-19. Finalmente, examinou-se o efeito do gênero na relação entre atividade física e variáveis dependentes. Um instrumento de pesquisa global foi utilizado neste estudo, no qual um total de 1.400 adultos turcos participaram. Os resultados desta investigação demonstram que existem diferenças significativas em atividade física, esperança, depressão, ansiedade e estado de enfrentamento de adultos por sexo. Não houve diferença significativa entre os sexos para os escores de esperança. Além disso, a atividade física influenciou diretamente o enfrentamento (β = 0,10), a esperança (β = 0,12) e a ansiedade (β = -0,08). A esperança influenciou direta e positivamente o enfrentamento (β = 0,45) e influenciou direta e negativamente a ansiedade (β = -0,25) e a depressão (β = -0,28). Além disso, o gênero não afetou diretamente a atividade física, mas o gênero foi associado à diminuição do enfrentamento e ao aumento da depressão e ansiedade. Finalmente, o gênero não teve efeito sobre a relação entre atividade física e esperança, enfrentamento, depressão, ansiedade (p > 0,01). Estes resultados apoiam a importância crítica da atividade física e da esperança ao lidar com COVID-19 sem efeitos de gênero.

Resumen: Existe la necesidad de comprender mejor las relaciones entre COVID-19, los comportamientos de afrontamiento, la actividad física y el estrés, y el impacto de COVID-19 en la forma de vida. Se utilizó un diseño de estudio transversal para examinar la actividad física del adulto, la esperanza, la depresión, la ansiedad y el estado de afrontamiento por género durante COVID-19 y para determinar los efectos de la actividad física, la esperanza, la depresión, y ansiedad en el afrontamiento de COVID-19. Finalmente, se examinó el efecto del género en la relación entre la actividad física y las variables dependientes. En este estudio se utilizó un instrumento de investigación global, en el que participaron un total de 1.400 adultos turcos. Los resultados de esta investigación demuestran que existen diferencias significativas en la actividad física, la esperanza, la depresión, la ansiedad y el estado de afrontamiento de los adultos por sexo. No hubo diferencias significativas entre los sexos para las puntuaciones de esperanza. Además, la actividad física influyó directamente en el afrontamiento (β = 0,10), la esperanza (β = 0,12) y la ansiedad (β = -0,08). La esperanza influyó directa y positivamente en el afrontamiento (β = 0,45) e influyó directa y negativamente en la ansiedad (β = -0,25) y la depresión (β = -0,28). Además, el género no afectó directamente a la actividad física, pero el género se asoció con una disminución del afrontamiento y a un aumento de la depresión y la ansiedad. Finalmente, el género no tuvo ningún efecto sobre la relación entre la actividad física y la esperanza, el afrontamiento, la depresión, la ansiedad (p > 0,01). Estos resultados respaldan la importancia crítica de la actividad física y la esperanza cuando se trata de COVID-19 sin efectos de género.

Development and internal validation of a clinical prediction model for spontaneous abortion risk in early pregnancy

Abstract Objective: This study aimed to develop and internally validate a prediction model for estimating the risk of spontaneous abortion in early pregnancy. Methods: This prospective cohort study included 9,895 pregnant women who received prenatal care at a maternal health facility in China from January 2021 to December 2022. Data on demographics, medical history, lifestyle factors, and mental health were collected. A multivariable logistic regression analysis was performed to develop the prediction model with spontaneous abortion as the outcome. The model was internally validated using bootstrapping techniques, and its discrimination and calibration were assessed. Results: The spontaneous abortion rate was 5.95% (589/9,895) 1. The final prediction model included nine variables: maternal age, history of embryonic arrest, thyroid dysfunction, polycystic ovary syndrome, assisted reproduction, exposure to pollution, recent home renovation, depression score, and stress score 1. The model showed good discrimination with a C-statistic of 0.88 (95% CI 0.87‒0.90) 1, and its calibration was adequate based on the Hosmer-Lemeshow test (p = 0.27). Conclusions: The prediction model demonstrated good performance in estimating spontaneous abortion risk in early pregnancy based on demographic, clinical, and psychosocial factors. Further external validation is recommended before clinical application.

Clinical and radiographic evaluation of Bio-Oss granules and Bio-Oss Collagen in the treatment of periodontal intrabony defects: a retrospective cohort study

Abstract Objective This retrospective study aimed to analyze the clinical efficacy of two regenerative surgical methods — Bio-Oss granules combined with barrier membranes and Bio-Oss Collagen alone — and to help clinicians achieve better periodontal regeneration outcomes in the specific periodontal condition. Methodology Patients who underwent periodontal regeneration surgery from January 2018 to April 2022 were retrospectively screened, and their clinical and radiographic outcomes at 6 months postoperatively were analyzed. The probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), gingival recession (GR), distance from the cemento-enamel junction to the bottom of the bone defect (CEJ-BD), and depth of intrabony defects (INFRA) were recorded before the operation (T0) and 6 months after it (T1), and subsequently compared. Results In total, 143 patients were included — 77 were placed in the Bio-Oss group and 66 were placed in the Bio-Oss Collagen group. All indicators, including PD and CAL at T1, showed significant differences compared to baseline, for both groups (P<0.001). PD reduction was greater in the group receiving the Bio-Oss Collagen treatment (P=0.042). Furthermore, in cases when the baseline PD range was 7-11 mm and the age range was 35-50 years, PD reduction was more significant for patients receiving the Bio-Oss Collagen treatment (P=0.031, 0.023). A linear regression analysis indicated that postoperative PD and CAL were positively correlated with baseline values, and that the efficacy tended to decrease with increasing age. Conclusion Both the use of Bio-Oss Collagen alone and the use of Bio-Oss granules combined with barrier membranes resulted in significant effects in the treatment of periodontal intrabony defects. The Bio-Oss Collagen treatment generated more improvements in PD than the Bio-Oss granules combined with barrier membranes, particularly within the baseline PD range of 7-11 mm and the 35-50 years age group. Additionally, age was the main factor influencing the effectiveness of regenerative surgery for intrabony defects: older individuals exhibited fewer improvements.

Serum interleukin-33 combined with FEF75% z-score and FeNO improves the diagnostic accuracy of asthma in children

Abstract Objective To investigate the diagnostic efficacy of serum IL-33 single indicator and combined indicators for asthma in children. Methods 132 children were initially diagnosed with asthma during acute exacerbation and 100 healthy children were included. Serum IL-33 concentration differences were compared between asthmatic and normal children. Correlations between IL-33 with pulmonary function parameters, FeNO, peripheral blood EOS counts and serum total IgE were analyzed in asthmatic children. ROC curves were used to assess IL-33 diagnostic efficacy and its combined indicators. To prevent overfitting of the predictive model, the hold-out cross-validation method was used. Results (1) Serum IL-33 concentrations were significantly higher in children with asthma than in normal children (p < 0.001). (2) IL-33 concentration was negatively correlated with FVC z-score, FEV1 z-score and FEF75% z-score in asthmatic children (p < 0.05). (3) The area under the ROC curve of IL-33 was 0.821, which was higher than those of FeNO, FVC z-score, and FEV1 z-score. (4) Cross-validation of the combined indicators showed that IL-33 significantly improved asthma diagnostic efficacy. The combination of IL-33, FEF75% z-score, and FeNO showed the highest diagnostic efficacy, with the AUC, sensitivity, and specificity of the combined indicator being 0.954, 90.1%, and 89. 0%, respectively, and good extrapolation of the predictive model. Conclusion Serum IL-33 is higher in children with asthma and increases with the severity of pulmonary ventilation obstruction. A single indicator of serum IL-33 demonstrates moderate diagnostic accuracy, and its combination with FEF75% z-score and FeNO significantly improves the diagnostic accuracy in childhood asthma.